Optimal follow-up after acute pulmonary embolism: a position paper of the European Society of Cardiology Working Group on Pulmonary Circulation and Right Ventricular Function, in collaboration with the European Society of Cardiology Working Group on Atherosclerosis and Vascular Biology, endorsed by the European Respiratory Society.

This position paper provides a comprehensive guide for optimal follow-up of patients with acute pulmonary embolism (PE), covering multiple relevant aspects of patient counselling. It serves as a practical guide to treating patients with acute PE complementary to the formal 2019 European Society of Cardiology guidelines developed with the European Respiratory Society. We propose a holistic approach considering the whole spectrum of serious adverse events that patients with acute PE may encounter on the short and long run. We underline the relevance of assessment of modifiable risk factors for bleeding, of acquired thrombophilia and limited cancer screening (unprovoked PE) as well as a dedicated surveillance for the potential development of chronic thromboembolic pulmonary hypertension as part of routine practice; routine testing for genetic thrombophilia should be avoided. We advocate the use of outcome measures for functional outcome and quality of life to quantify the impact of the PE diagnosis and identify patients with the post-PE syndrome early. Counselling patients on maintaining a healthy lifestyle mitigates the risk of the post-PE syndrome and improves cardiovascular prognosis. Therefore, we consider it important to discuss when and how to resume sporting activities soon after diagnosing PE. Additional patient-relevant topics that require Focused counselling are travel and birth control.

Extended Anticoagulant Treatment with Full- or Reduced-Dose Apixaban in Patients with Cancer-Associated Venous Thromboembolism: Rationale and Design of the API-CAT Study.

Cancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding. The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5 mg twice daily [bid]) is noninferior to a full-dose regimen of apixaban (5 mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed ≥6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism. API-CAT is an international, randomized, parallel-group, double-blind, noninferiority trial with blinded adjudication of outcome events. Consecutive patients are randomized to receive apixaban 2.5 or 5 mg bid for 12 months. The primary efficacy outcome is a composite of recurrent symptomatic or incidental VTE during the treatment period. The principal safety endpoint is clinically relevant bleeding, defined as a composite of major bleeding or nonmajor clinically relevant bleeding. Assuming a 12-month incidence of the primary outcome of 4% with apixaban and an upper limit of the two-sided 95% confidence interval of the hazard ratio <2.0, 1,722 patients will be randomized, assuming an up to 10% loss in total patient-years (ß = 80%; α one-sided = 0.025). This trial has the potential to demonstrate that a regimen of extended treatment for patients with CT beyond an initial 6 months, with a reduced apixaban dose, has an acceptable risk of recurrent VTE recurrence and decreases the risk of bleeding.

Effective diagnosis and treatment of pulmonary embolism: Improving patient outcomes.

Pulmonary embolism can be life threatening and difficult to diagnose as signs and symptoms are not specific. European guidelines recommend stratification of pulmonary embolism by risk of early mortality. Patients with suspected pulmonary embolism should be assessed for clinical probability of pulmonary embolism using a validated risk score. A low or intermediate clinical probability plus a negative high-sensitivity D-dimer test excludes pulmonary embolism. Anticoagulation is indicated in patients with a positive multidetector computed tomography or high-probability lung scan. An important part of the management of patients with pulmonary embolism has traditionally been anticoagulant treatment with parenteral heparins and oral vitamin K antagonists. Although effective, this dual-drug approach is associated with limitations. Direct oral anticoagulants that may overcome some of these problems have been tested in phase III clinical trials for the treatment of venous thromboembolism. Of these, rivaroxaban and apixaban have demonstrated non-inferiority to standard therapy when given as single-drug approaches for venous thromboembolism treatment, and provided significant reductions in major bleeding rates. Dabigatran and edoxaban were non-inferior to standard therapy when given as part of a dual-drug approach after initial parenteral anticoagulation, and reduced clinically relevant bleeding rates. There may be a benefit to extended anticoagulation with direct oral anticoagulants for the prevention of recurrent venous thromboembolism. Registry studies will provide more information on the use of these agents in real-world populations. Accurate diagnosis and risk stratification of patients with pulmonary embolism, together with simplified anticoagulation therapy, is likely to improve outcomes.